Microvascular and cellular responses in the optic nerve of rats with acute experimental allergic encephalomyelitis (EAE)

Brain Pathol. 1998 Jul;8(3):475-86. doi: 10.1111/j.1750-3639.1998.tb00169.x.


The optic nerve of rats with EAE was examined at various times to determine the integrity of the blood-brain barrier (BBB) and to assess monocyte-macrophage, T cell, and microglial responses. In naive control animals, leakage of horseradish peroxidase (HRP) and the presence of cells expressing major histocompatibility complex (MHC) class II antigen were evident in the meninges of the retrobulbar optic nerve. In rats with EAE, microglia in the region of the lamina cribrosa and in the regions adjacent to the meninges became activated from day 7 to 8 postinduction (pi). HRP leakage was also evident in the region of the lamina cribrosa from day 7 to 8 pi. On day 8 pi, infiltration of inflammatory cells and Monastral blue leakage were apparent in the myelinated region of the optic nerve. The intensity of these cellular and vascular changes peaked at day 12 pi, when signs of clinical disease became manifest. Monocytes-macrophages expressing MHC class II and the ED1 antigen, together with lymphocytes expressing the alphabetaT cell receptor, constituted the major proportion of cells associated with inflammatory lesions. Thus: (i) the inherent weakness of the BBB as well as the presence of both antigen (myelin) and MHC class II+ cells in the retrobulbar optic nerve are likely susceptibility factors for the frequent involvement of this region in EAE and multiple sclerosis; and (ii) activation of microglia occurs early in the pathogenesis of experimental optic neuritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Coloring Agents
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Histocompatibility Antigens Class II / metabolism
  • Horseradish Peroxidase
  • Immunohistochemistry
  • Indoles
  • Lymphocyte Subsets / immunology
  • Macrophages / immunology
  • Male
  • Microcirculation / pathology
  • Microglia / metabolism
  • Monocytes / immunology
  • Myelin Basic Protein / pharmacology
  • Myelin Sheath / pathology
  • Optic Nerve / blood supply*
  • Optic Nerve / immunology
  • Optic Nerve / metabolism
  • Optic Nerve / pathology*
  • Organometallic Compounds
  • Rats
  • Rats, Inbred Lew
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Time Factors


  • Coloring Agents
  • Histocompatibility Antigens Class II
  • Indoles
  • Myelin Basic Protein
  • Organometallic Compounds
  • Receptors, Antigen, T-Cell, alpha-beta
  • copper phthalocyanine
  • Horseradish Peroxidase